三氧化二砷对狼疮小鼠存活率和自身免疫反应的影响(英文)

Effects of arsenic trioxide on survival rate and autoimmune responses of lupus mice

目的探讨三氧化二砷(ATO)在治疗系统性红斑狼疮中的应用价值并探讨其作用机制。方法① BXSB狼疮小鼠随机分为ATO治疗组和对照组,每组17只。ATO治疗组隔日ip ATO0.4 mg·kg-1至d105,实验持续至d 210结束,观察两组小鼠的存活率,采用ELISA法检测小鼠血清IgG和抗ds-DNA抗体水平。②另外20只BXSB狼疮小鼠,同上分组处理,至d 90处死取脾和肾组织,提取总RNA,用RT-PCR方法检测脾和肾组织中干扰素γ(IFN-γ)mRNA的表达。结果至d210,ATO治疗组小鼠死亡8只,对照组死亡13只。至d90和d105,治疗组小鼠血清抗ds-DNA抗体(A450 nm)分别为0.335±0.011和0.223±0.017,对照组分别为0.688±0.016和0.683±0.014。至d90 ATO治疗组小鼠脾和肾组织IFN-γ mRNA表达较对照组亦明显下降。至d 105,ATO治疗组血清IgG水平较对照组明显下降,分别为(4.9±1.3)和(6.9±1.0)g.L-1。结论 ATO可提高BXSB狼疮小鼠的存活率,降低血清IgG和抗ds-DNA抗体水平,抑制脾和肾组织IFN-γ mRNA的表达。

AIM To evaluate the value of arsenic trioxide （ATO） in the treatment of systemic lupus erythematosus and to investigate its mechanism. METHODS ① Thirty four BXSB lupus mice were averagely and randomly divided into ATO treated group and control group. The mice of ATO treated group were given （ip） ATO 0.4 mg· kg^-1 every other day until d 105 and the observation was ended on d 210. The survival rate of mice was recorded, and the levels of serum IgG and anti-dsDNA antibody were measured with enzymelinked immunosorbent assay. mice were also divided into Other 20 BXSB lupus groups and treated as above and sacrificed on d 90. The spleen and kidneys of each mouse were removed and total RNA was extracted. The levels of interferon-γ/ （IFN-γ） mRNA in renal and spleen tissues were measured by using reverse transcription polymerase chain reaction. RESULTS Up to d 210, 8 mice died in ATO treated group and 13 died in control group. On d 90 and d 105, the average levels of serum anti-dsDNA antibody （ A450 nm ） were （0.335 ±0.011） and （0.223 ±0.017） in ATO treated group, and （0.688 ±0.016） and （0.683 ± 0.014） in control group. On d 90, the expressions of IFN-γmRNA in spleen and renal tissues of ATO treated group were significantly lower than that of control group. On d 105, the serum level of IgG was much lower in ATO treated group than that in control group, which were （4.9±1.3） and （6.9±1.0）g·L^-1, respectively. CONCLUSION ATO elevates the survival rate, lowers the serum levels of IgG and anti-dsDNA antibody, and depresses the expression of IFN-γ mRNA in spleen and kidney tissues of BXSB mice.